A major goal in AIDS research is the development of new markers to monitor HIV-1 disease progression and drug therapy, particularly during the clinically latent period when it is difficult to detect HIV-1 or infected cells in the peripheral blood. Recent observations using fresh lymphoid tissues have demonstrated that during this period, HIV-1 accumulates and actively replicates in lymphoid organs. Development of an imaging agent for HIV-1 disease would provide a non-invasive technique to localize and quantitate HIV-1 virions and productively infected cells in lymphatic tissues and other sites in the body. In this Phase I study, they will develop two radioiodinated CD4-immunoglobulin chimeric proteins as novel in vivo imaging agents for HIV-1 disease. The two recombinant proteins are: CD4-gamma2, a homodimer containing two chains of a CD4-human IgG2 heavy chain fusion protein, and CD4-IgG2, a heterotetramer containing two chains of a CD4-human IgG2 heavy chain fusion protein and two chains of a CD4-human kappa light chain fusion protein. The major advantage of CD4-based molecules over monoclonal antibodies as candidate imaging agents is that CD4 binds with high affinity to the HIV-1 envelope glycoprotein gp120/gp41 of all strains of the virus. The development of an in vivo imaging agent for HIV-1 disease will likely provide new insights into the pathogenesis of this disease and be a valuable tool in the management of HIV-1 infected individuals.